Method of making a flexible electrode bio-probe assembly

ABSTRACT

A method of producing an electrode brain probe assembly, using a flexible substrate comprising a polymeric layer bearing a conductive material coating. Photolithography and electroplating are used to form a set of contacts and conductors on the polymeric layer of the flexible substrate. Also, the flexible substrate is shaped to have a distal end and to be at least 5 mm long, but less than 5 mm wide and less than 1 mm thick.

RELATED PATENT APPLICATIONS

The present application is a continuation in part of application Ser.No. 09/653,489, filed Aug. 31, 2000, now U.S. Pat. No. 6,495,020 whichis, in turn, a divisional of application Ser. No. 09/518,006, filed Mar.2, 2000, now U.S. Pat. No. 6,368,147 issued Jun. 25, 2002.

STATEMENT OF GOVERNMENT SUPPORT

This invention was made with government support under 2R44NS33427awarded by the SBIR. The government has certain rights in the invention.

BACKGROUND OF THE INVENTION

The present invention is a method of making a flexible brain probeassembly.

Creating a probe that contacts the brain tissue represents a challengeto researchers. Researchers typically wish to measure electricalactivity at specific sites within the brain that share a well-definedphysical relationship to one another. Probes produced byphotolithographic techniques, such as the probe designed by personnel atthe University of Michigan that is known in the industry and researchcommunity as the “University of Michigan Probe,” permit the accurateplacement of electrode sites that are sufficiently small to permit themeasurement of electrical activity at a specific set of predefined siteswithin the brain. Unfortunately, the desire to use photolithography hasprompted the use of silicon as a substrate. Because this material isquite brittle, the use of it creates a risk of breakage inside thebrain, endangering the subject or patient and limiting the insertionstrategies available to researchers. Moreover, the use of siliconprevents the University of Michigan probe from moving with the brain,which does move about slightly within the skull. In addition, silicon issubject to some restoring force, which tends to cause a silicon probe tomigrate over time. Both of these drawbacks have the potential result ofcausing trauma to the brain tissue.

Another type of probe that is currently available includes a set ofinsulated wires having laser created apertures exposing electrode sites.Although this type of probe is useful for many applications, it does notyield the precision or the freedom of electrode placement that theUniversity of Michigan probe permits.

A nerve cuff is a device for wrapping about a nerve to electricallystimulate and/or receive electric signals from the nerve. The productionof nerve cuffs has also been problematic as the fine scale of the neededfeatures has been difficult to produce on a flexible substrate capableof being wrapped about a nerve.

What is needed but not yet available is an electrode probe and method ofmaking the same that affords unconstrained and accurate placement of theelectrodes, but offers flexibility and robustness and is thereby lesssusceptible to breakage than currently available probes.

SUMMARY

In a first separate aspect, the present invention is a method ofproducing an electrode bio-probe assembly, using a flexible substratecomprising a polymeric layer bearing a conductive material coating.Photolithography and electroplating are used to form a set of contactsand conductors on the polymeric layer of the flexible substrate. Also,the flexible substrate is shaped to have a distal end and to be greaterthan 5 mm long, less than 5 mm wide and less than 1 mm thick.

In a second separate aspect, the present invention is a method ofproducing a nerve cuff assembly for application to a target nerve. Themethod includes the use of photolithography and electroplating to form aset of contacts and conductors on the polymeric layer of a flexiblesubstrate having a polymeric layer and bearing a conductive materialcoating. The flexible substrate is sized and shaped to fit about thetarget nerve.

The foregoing and other objectives, features and advantages of theinvention will be more readily understood upon consideration of thefollowing detailed description of the preferred embodiment(s), taken inconjunction with the accompanying drawings.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a side view of the connector of FIG. 1, shown attached to askull and connected to a brain probe that is embedded in brain tissue.

FIG. 2 is an exploded perspective view of a connector according to thepresent invention.

FIG. 3 is a perspective view of the connector of FIG. 1, with the twoconnector halves mated.

FIG. 3A is a perspective of a portion of an alternative embodiment toFIG. 1, showing the differing structure of the alternative embodiment.

FIG. 4 is a greatly expanded plan view of a connective surface of theconnector of FIG. 1.

FIGS. 5a-5 g is a series of greatly enlarged side cross-sectional viewsshowing the construction of the connector flex circuit, or thin film,which may include the brain probe flex circuit of FIG. 1 in a singleunit.

FIG. 6 shows an expanded flexible brain probe, according to the presentinvention, and a tool for pushing this brain probe through brain tissue,also according to the present invention.

FIG. 7 shows the flexible brain probe and tool of FIG. 6, in a 180°rotated view.

FIG. 8 shows a nerve cuff produced in accordance with the presentinvention, wrapped about a nerve.

FIG. 9 shows a nerve cuff produced in accordance with the presentinvention.

FIG. 10 shows an alternative embodiment of a nerve cuff produced inaccordance with the present invention.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENT

Referring to FIG. 1, a percutaneous connector 10 is screwed into theskull 1 and is connected, by way of a multi-conductor microcable 20, toa brain probe 24 that passes through an aperture 2 in the skull, throughthe dura 4 (and into the brain 6), for measuring brain activity at aspecific set of points.

Referring to FIGS. 2, 3 and 3A a percutaneous connector 10 according tothe present invention includes a male-half 12, a female-half bracket 14and a female-half flex circuit (or flexible polymer) connective assembly16 bearing a set of contacts 17 and conductive traces 19. Amulti-conductor microcable 20 forms a portion of assembly 16 and isthreaded through an aperture 22 in bracket 14. The microcable 20attaches to and extends traces 19 to brain probe 24. As shown in FIG. 3ain an alternative embodiment, a connective assembly 16′ includes amicrocable 20′ that includes a brain probe 24′ as a unitary part of itsconstruction. The male-half includes a resilient clip portion 28, theexterior of which is covered with a flex-circuit 34 bearing a set ofcontacts 36 (matching the arrangement of contacts 19) and conductivetraces 38.

A first prong 40 and a second prong 42, which is physically coincidentwith an op-amp housing, partially defines clip portion 28. A user cangrasp male-half 12 by the first and second prongs 40 and 42 to squeezethese prongs 40 and 42 together. The male-half 12 can then be insertedinto the female-half 14, without exerting pressure against female-half14, which could cause pain or tissue trauma to the patient or testsubject. Finally, the user releases prongs 40 and 42 so that theresiliency of clip 28 will force each exterior side of clip 28, andtherefore contacts 36, to touch the contacts 17 in female-half 14.

Referring to FIG. 4 and 5a-5 g, contacts 17 and traces 19 are made ofconductive material, such as a metal (copper, gold or sliver) or aconductive polymer that has been deposited and etched on top of alaminate having a layer of dielectric substrate 50 and a base layersilicone 70 or some other biocompatible, compliant material.Semicircular isolation cuts 48 through the layers 50 and 70 (in analternative preferred embodiment only layer 50 is cut through by thelaser) positionally decouple a first contact 17 a from neighboringcontacts 17 b, 17 c and 17 d, permitting contact 17 a to be depressedinto the spongy layer of silicone 70 without pulling down theneighboring contacts 17 b, 17 c and 17 d. This independentdepressability causes the protrusional misalignment of contacts 17 and36 to be forgiven.

The miniature scale that is made possible by the use of photolithographyand flex circuit technology, as described above, facilitates a furtheradvantage that may be realized as part of the present invention. This isthe placement of op amps in extremely close proximity to contacts 36.For connectors in which the contacts are spread apart from each other,it is necessary to gather together conductive paths from all thedifferent contacts prior to sending them all to a set of op amps.Because contacts 36 are all so close together, traces 38 are routed to aset of op amps 44, that are about 0.5 cm away and are housed in thesecond prong 42, which doubles as an op amp housing. As a result, signalline noise and cross talk are minimized.

Referring to FIGS. 5a-5 g, the photolithography process for making thebrain probe 24 and the contacts of the percutaneous probe contactstructure 30 are quite similar, except that different materials may beused and the percutaneous probe contact structure 30 includes a baselayer of silicone 70, that is only shown in FIG. 5g, for the sake ofsimplicity. Referring specifically to FIG. 5a, the photolithographyprocess begins with a layer of dielectric substrate 50, the compositionof which is discussed below, that is coated with a base layer ofconductive material 52, such as a titanium-gold-titanium sandwich. FIG.5b shows the structure of FIG. 5a, which at this point has been coveredwith a layer of photo resist material 54, typically applied byspin-coating. FIG. 5c shows the effect of exposing the photo resistmaterial to a pattern of light and washing off the exposed (or notexposed if a negative process is used) material with a developing agent.Next, as shown in FIG. 5d, additional conductive material (typicallycopper) is built up on the exposed base layer 52, typically throughelectrolysis. As shown in FIG. 5e, the remaining photo resist material54 is washed off with a solvent and a layer of dielectric (andpermanent) photo resist 58 is applied and patterned, via exposure to apattern of light and subsequent washing with a developing agent orsolvent. Then, additional electrolytic plating is performed (FIG. 5f) tocreate a contact 60 and the substrate is cut with an nd:YAG laser toform a kerf or cut 62. When the process shown in FIGS. 5a-5 g is forproducing connector 10, cut 62 is the same as isolation cut 48. When theprocess shown in FIGS. 5a-5 g is for producing a brain probe 24, cut 62separates a first brain probe 24 from a wafer or thin plastic film uponwhich several brain probes have been etched. In contrast to thesituation with respect to silicon, which may be separated by etching, itappears that no etching process has been developed for cutting thematerials used for substrate 50, which are discussed below.

The dielectric substrate 50 that is used for the brain probe 24 ispreferably a polymer material having a high glass transitiontemperature, high tensile strength and low elasticity. Morespecifically, substrate 50 may be made of polyether sulfone, polyimideor other material having the desired characteristics. If polyimide isused, it should be coated or treated so that it does not dissolve in thebody's interstitial fluid, or used for a probe that is not to beimplanted for long enough for the polyimide to dissolve. Photo resistmaterial 54 may be a photosensitive acrylate, polyether or polyurethane,preferably having a high molecular weight. Permanent photo resist 58 maybe a permanent polyimide, a type of material that is widely availablefrom well-known photo resist companies. These companies typically sell awet etch agent specifically designed to etch each permanent polyimidephoto resist that they sell.

Brain probe 24 includes three prongs 72. Each prong 72 is on the orderof 15 mm long, 3 mm wide and 0.3 mm thick. During the manufacturingprocess each prong 72 is sharpened so that it may more easily be driventhrough the brain tissue. It is desirable that a brain probe, if it isto be implanted for a period of time on the order of weeks, be verypliable, so that it may conform to the brain tissue surrounding it andnot cause further damage by pressing against the delicate brain tissue.If the brain probe is to be installed by being driven through braintissue, however, it must be fairly rigid, requiring a strength layer,such as layer of steel or some other resilient material, laminatedbeneath layer 70, typically before the production process begins.

Referring to FIGS. 6 and 7, in one preferred embodiment a brain probe 80is constructed to be very pliable. In brain probe 80 only a single point90 is provided, in order to facilitate the placement process, which iscomplicated by the three-pointed (or pronged) embodiment shown in FIG.3. FIG. 6 shows brain probe 80 in tandem with a placement tool 84, whichengages brain probe 80 at aperture 86. Placement tool 84 is used to pushthe point of probe 80 through brain tissue 6 (FIG. 1) , to the point atwhich contact with brain tissue 6 is desired. For chronically implantedbrain probes, the quality of being pliable may be very important, toavoid the damage that a rigid brain probe could inflict with patientmovement. The brain moves about in the skull with patient head movement,and colliding with a rigid probe could easily damage the soft braintissue.

In the embodiment of FIG. 6, electrodes 17 are from 12.56 square micronsto 300 microns in surface area. In one preferred embodiment electrodes17 are 176 have a surface area of 176 square microns. The probe 80,itself is at least 5 mm long, and no more than 5 mm wide and 1 mm thick.In the preferred embodiment shown, cuts 48 are through-cuts and permittissue ingrowth , which along with the tissue ingrowth at aperture 86helps to anchor brain probe 90, in the brain tissue. In an alternativepreferred embodiment, cuts 48 are not present.

Referring to FIGS. 8, 9 and 10, the method of construction shown inFIGS. 5a-5 g is used for the production of nerve cuffs 100, 110 and 120.A nerve cuff is a device that is adapted to be wrapped around a nerve130 and used to electrically stimulate the nerve 130. In nerve cuff 110a set of twelve contacts 112 have been created through photolithography.In nerve cuff 120 four complex contacts 122, designed forcircumferentially contacting a nerve have been created by way ofphotolithography.

The terms and expressions which have been employed in the foregoingspecification are used as terms of description and not of limitation,and there is no intention, in the use of such terms and expressions, ofexcluding equivalents of the features shown and described or portionsthereof, it being recognized that the scope of the invention is definedand limited only by the claims which follow.

What is claimed is:
 1. A method of producing an electrode brain probe assembly, comprising the steps of: a) providing a flexible substrate comprising a polymeric layer and bearing a conductive material coating; b) patterning and plating said conductive material to form a set of contacts and conductors on said polymeric layer of said flexible substrate; and c) shaping said flexible substrate so that it has a distal end, is greater than 5 mm long, less than 5 mm wide and less than 1 mm thick.
 2. The method of claim 1 further comprising shaping said flexible substrate so that it is pointed at said distal end.
 3. The method of claim 1 further comprising creating a through hole at said distal end of said electrode brain probe assembly, thereby permitting the use of a placement device to push said bio-probe into delicate soft tissue, such as brain tissue.
 4. The method of claim 1 wherein more than one electrode probe assemblies are produced on a single substrate and including the step of dividing said substrate to produce said more than one electrode probe assemblies.
 5. The method of claim 4 wherein a laser beam is used to divide said substrate into said more than one probe assemblies.
 6. The method of claim 1 wherein said flexible polymer substrate is comiprised of a layer of polyether sulfone.
 7. The method of claim 1 wherein said flexible polymer substrate is comprised of a layer of polyimide.
 8. The method of claim 1 wherein said conductive material is a metal.
 9. The method of claim 1 wherein said conductive material is a conductive polymer.
 10. The method of claim 1 wherein said flexible polymer substrate is comprised of a layer of liquid crystal polymer. 